Autoantibodies to the insulin receptor occur in patients with insulin resistance as well as patients with hypoglycemia. We have carried out in vitro and in vivo studies of the effects of anti-receptor antibodies to mimic or antagonize insulin action. We are attempting to address the question of what determines the balance between the insulinomimetic and insulin antagonistic actions of anti-receptor antibodies. We have obtained B-lymphocytes from the peripheral blood and bone marrow from patients with anti-receptor antibodies in an effort to establish hybridomas which would synthesize anti-receptor antibodies in vitro. These monocional antibodies would be extremely useful as probes of receptor structure.